Thrombus Formation from Disease or Surgery
Blood clots, or thrombi, form at the sites of blood vessel injury. The clinical manifestations of pathological thrombosis or thrombotic disease are extremely diverse and include deep vein thrombosis (DVT), and arterial and venous thrombosis. Thromboembolism and thrombotic complications of other vascular disease (e.g., atherosclerosis) can result in occlusion of major arteries leading to organ ischemia and the attendant life-threatening conditions such as cerebrovascular accident (stroke), myocardial infarction, etc.
In addition, invasive surgical procedures, including but not limited to balloon angioplasty, and organ transplantation (both natural and artificial), can trigger thrombus formation. For example, balloon angioplasty, a procedure used to clear occluded arteries, can actually injure the arterial vessel wall, triggering reocclusion by new thrombus deposition. One report states that percutaneous transluminal coronary angioplasty remains plagued by a 25-35% frequency of reocclusion of the vessel. Gimple, L. W., et al., Circulation, 86:1536-46 (1992). See also Sarembock, I. J., et al., Circulation, 80:1029-40 (1989); and Ip, J. H., et al., JACC, 17:77B-88B (1991). In fact, one report states that "the mechanism of angioplasty, involving in most cases endothelial damage and plaque fracture or dissection [ref.], is very similar to the process that leads to the acute ischemic syndromes." Tenaglia, A. N., Ann. Rev. Med., 44:465-79, 466 (1993).
Since systemic treatment with anticoagulants such as heparin and coumarin have been shown to have little or no effect in preventing post-angioplasty reocclusion (Ip, J. H., et al., JACC, 17:77B-88B (1991)), and since such anticoagulant treatments often risk systemic hemorrhage in patients (Physicians' Desk Reference, 47th Ed., Medical Economics Data (1993)), new site-specific methods of treatment to inhibit or interfere with thrombus formation, both in the case of pre-existing vascular disease and for invasive surgical procedures, would be useful.